1. Prior Art
Pepstatins are pentapeptides having the following general formula: EQU R-Val-Val-X-Ala-X
wherein R stands for an acyl group, Val for L-valine, Ala for L-alanine, and X for (CH.sub.3).sub.2 CH--CH.sub.2 --CH(NH.sub.2)--CH(OH)--CH.sub.2 --COOH, which are bound through amide linkages. The pepstatins include pepstatin A (R=(CH.sub.3).sub.2 CH--CH.sub.2 --CO--), pepstatin B (R = CH.sub.3 --(CH.sub.2).sub.4 --CO--), pepstatin C(R = (CH.sub.3).sub.2 CH--(CH.sub.2).sub.2 --CO--), and so on, according to the acyl group in the molecule. Pepstanone, in which the terminal X is (CH.sub.3).sub.2 CH--CH.sub.2 --CH(NH.sub.2)--CO--CH.sub.3, also belongs to this group.
Pepstatin was discovered by Umezawa et al. Similar substances were found by others later. These are all protease inhibitors produced by strains of Streptomyces and having high inhibitory activity on acid proteases, particularly on pepsin. It has been reported that pepstatin A takes effect on gastric ulcers clinically.
In Japanese Patent Publication 47-8996 and in U.S. Pat. No. 3,740,319 issued June 19, 1973, there is described and claimed a process for the production of a pepstatin characterized by cultivating a pepstatin-producing strain of Streptomyces such as Streptomyces testaceus MC144-Cl (ATCC 21469) or Streptomyces argenteolus var. toyanakensis MC210-Al (ATCC 21468) in a nutrient medium containing a carbon source such as glucose, starch or fat and a nitrogen source such a peptone, meat extracts, casein, soy bean meal or corn steep liquor under aerobic conditions.
The MC numbers are those assigned to the respective Streptomyces strains by the applicants themselves; and the ATCC numbers are those assigned to such strains by the American Type Culture Collection, in which these strains have been respectively deposited. The characteristics and other details of these two strains are set forth in the aforementioned U.S. Pat. No. 3,740,319, the disclosure of which is hereby fully incorporated in the present application by reference.